N Nakano

Regulation of Human B Cell Differentiation: Molecular Structure and Immunological Functions of Human B Cell Differentiation Factor (BSF-2)

Regulation of human B cell differentiation into antibody-secreting cells was studied. By utilizing monoclonal antibodies, B cells can be isolated into three subpopulations with respect to their activation stage: resting B cells, activated B cells, and B cells at the final differentiation stage. Anti-IgM together with BSF-1 activate resting B cells into the activated stage and activated B cells secrete BCGF and become responsive to BCGF. Then, BCDF (BSF-2) induces Ig secretion in activated B cells. cDNA for BSF-2 has been cloned and recombinant BSF-2 induced Ig secretion in B lymphoblastoid cells as well as in normal cells. The amino acid sequence deduced from the cDNA sequence does not have any homology with other lymphokines. Patients with cardiac myxoma often show autoantibody production. The result showed that cardiac myxoma cells secrete large amounts of BSF-2, indicating that constitutive production of BSF-2 in vivo may be responsible for autoantibody production.

Regulation of human B lymphocytes differentiation: Characterization of B cell stimulatory factors

B lymphocytes originate from pluripotent hematopoietic stem cells and differentiate into antibody producing cells through several distinct differentiation stages. Commitment of the antigen specificity in each B cell clone occurs at the stage of pre B cells by two step DNA rearrangements including V, D and J segments, i.e. from DJ joining to the functional VDJ formation (1). Following the rearrangement of heavy chain genes, light chain gene rearrangements occur (2) and 7S IgM molecules are expressed as antigen receptors on the surface of mature B cells. A given antigen selects a B cell clone with a matched receptor and activates this clone into antibody producing cells under the influence of helper T cells.

Regulation of growth and differentiation of human B cells

Activation process of B lymphocytes into immunoglobulin (Ig)-secreting cells can be dissected into three steps, i.e., activation, proliferation and differentiation (1–3). It has been demonstrated by several investigators that B cell specific growth and differentiation factors are involved in the process of proliferation and differentiation of activated B cells (4–10). The presence of two different kinds of B cell growth factors, BCGF-I or BSF-pI and BCGF-II, was reported in human (11) as well as in murine systems (12). BCGF-I induces proliferation of anti-IgM-stimulated human or murine B cells as well as SAC (Staphylococcus aureus Cowan I)-stimulated human B cells. Activated but not resting B cells are able to adsorb the activity of BCGF-I, suggesting the induction of the expression of receptors for BCGF-I on activated B cells. However, a recent study showed an increased expression of Ia antigen on resting B cells by stimulation with BCGF-I, suggesting the presence of BCGF-I receptors even on resting B cells, although BCGF-I induces proliferation only in activated B cells (13).